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Abstract Ni-based catalysts are highly reactive for dry reforming of methane (DRM) but they are prone to rapid deactivation due to sintering and/or coking. In this study, we present a straightforward approach for anchoring dispersed Ni sites with strengthened metal-support interactions, which leads to Ni active sites embedded in dealuminated Beta zeolite with superior stability and rates for DRM. The process involves solid-state grinding of dealuminated Beta zeolites and nickel nitrate, followed by calcination under finely controlled gas flow conditions. By combining in situ X-ray absorption spectroscopy and ab initio simulations, it is elucidated that the efficient removal of byproducts during catalyst synthesis is conducted to strengthen Ni–Si interactions that suppress coking and sintering after 100 h of time-on-stream. Transient isotopic kinetic experiments shed light on the differences in intrinsic turnover frequency of Ni species and explain performance trends. This work constructs a fundamental understanding regarding the implication of facile synthesis protocols on metal-support interaction in zeolite-supported Ni sites, and it lays the needed foundations on how these interactions can be tuned for outstanding DRM performance.

Abstract Internal combustion engine fueled by carbon-free hydrogen (H2-ICE) offers a promising alternative for sustainable transportation. Herein, we report a facile and universal strategy through the physical mixing of Pt catalyst with zeolites to significantly improve the catalytic performance in the selective catalytic reduction of nitrogen oxides (NO x ) with H2 (H2-SCR), a process aiming at NO x removal from H2-ICE. Via the physical mixing of Pt/TiO2 with Y zeolite (Pt/TiO2 + Y), a remarkable enhancement of NO x reduction activity and N2 selectivity was simultaneously achieved. The incorporation of Y zeolite effectively captured the in-situ generated water, fostering a water-rich environment surrounding the Pt active sites. This environment weakened the NO adsorption while concurrently promoting the H2 activation, leading to the strikingly elevated H2-SCR activity and N2 selectivity on Pt/TiO2 + Y catalyst. This study provides a unique, easy and sustainable physical mixing approach to achieve proficient heterogeneous catalysis for environmental applications.

The calculation method for negative skin friction of a single pile has not been unified yet. To improve the design and calculation level of the single pile under vertical load considering negative skin friction, the threshold limit value of pile skin friction was determined based on the effective stress method. The effects of relative displacement of pile-soil and pile depth on pile skin friction were analyzed, and a nonlinear calculation model for pile skin friction was established. The pile skin friction was divided into elastic and plastic states. In the elastic range, the friction is a quadratic function with the depth of the pile body; while in the plastic range, the friction is distributed linearly along the pile body, and the slope is the product of the effective weight of the soil around the pile and the negative friction coefficient. Consequently, the analytical solution of the pile skin friction for the corresponding pile section was acquired. Based on the theory of pile axial force calculation, a formula for calculating the axial force of a single pile under different distribution forms of pile lateral friction was obtained. The reliability, applicability, and practicality of this model were verified by measured data. Based on the calculated pile shaft axial force, the axial force of single pile with different distributions of skin friction was analyzed. This study has practical significance for fully utilizing the performance of pile foundations and improving the level of pile foundation design.

Fibroblast growth factor receptor 1 (FGFR1) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l−1, follicle-stimulating hormone (FSH) levels were 1.0 IU l−1, and testosterone levels were 1.3 nmol l−1. In contrast, the de novo group had LH levels of 0.2 IU l−1, FSH levels of 0.5 IU l−1, and testosterone levels of 0.9 nmol l−1, indicating milder hypothalamus–pituitary–gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

At present, there is an increasing demand for real-time communication and data transmission between the air and the sea. Therefore, it is important to study robust and reliable air-sea cross-domain communication technologies. However, due to the different characteristics of the two media and the impact of harsh environments, air-sea cross-domain communication channels are complex and varied, making it difficult to smoothly pass through the air-water interface. In order to better understand the development of air-sea cross-domain communication technologies, the current research on air-sea cross-domain communication was comprehensively summarized, and its working environment and development of communication technologies were explained. The technologies were divided into two categories: air-sea cross-domain link-level direct communication and air-sea cross-domain relay communication. Then, the research status, difficulties, and proposed solutions were summarized. Finally, future research directions were discussed. The research can help to promote the development of air-sea cross-domain communication technologies.

Abstract Waste oyster shells (WOS) have the potential to serve as a construction material, offering a sustainable alternative to traditional fine aggregates in the production of WOS concrete. This can play a critical role in reducing environmental issues resulting from the overexploitation of river sand and the haphazard disposal of WOS. Although existing research has predominantly focused on understanding the static mechanical characteristics of concrete when WOS is employed, the dynamic mechanical properties have still received less attention. To understand the impact of WOS as a substitute for fine aggregates on the dynamic mechanical properties of concrete, a series of tests employing Split Hopkinson Pressure Bar (SHPB) were carried out. The findings demonstrate that the peak stress and elastic modulus increase as the WOS substitution ratio (S r ) increases from 0 to 20% but exhibit an exponential decline as S r increases from 20 to 100%. This response can be explained by the joint effects of the pore-filling effect caused by WOS sand and the increasing air content caused by WOS sand. As S r increases from 0 to 20%, the pore-filling mechanism becomes predominant as the water absorption rate decreases slightly from 4.31 to 3.83%. However, for S r increasing from 20 to 100%, the negative influence of the air content becomes the primary contributing factor, where the water absorption rate increases from 3.83 to 14.68%. Furthermore, under the same impact pressure, the concrete with S r = 20% absorbed the most energy, providing the best dynamic mechanical performance. These findings highlight the potential use of WOS in concrete for improving its dynamic characteristics, promoting both sustainable construction and enhancing the material properties in impact-resistant structures.

Abstract Background Muscle satellite cells (MuSCs) exert essential roles in skeletal muscle adaptation to growth, injury and ageing, and their functions are extensively modulated by microenvironmental factors. However, the current knowledge about the interaction of MuSCs with niche cells is quite limited. Methods A 10× single‐cell RNA sequencing (scRNA‐seq) was performed on porcine longissimus dorsi and soleus (SOL) muscles to generate a single‐cell transcriptomic dataset of myogenic cells and other cell types. Sophisticated bioinformatic analyses, including unsupervised clustering analysis, marker gene, gene set variation analysis (GSVA), AUCell, pseudotime analysis and RNA velocity analysis, were performed to explore the heterogeneity of myogenic cells. CellChat analysis was used to demonstrate cell–cell communications across myogenic cell subpopulations and niche cells, especially fibro‐adipogenic progenitors (FAPs). Integrated analysis with human and mice datasets was performed to verify the expression of FGF7 across diverse species. The role of FGF7 on MuSC proliferation was evaluated through administering recombinant FGF7 to porcine MuSCs, C2C12, cardiotoxin (CTX)‐injured muscle and d‐galactose (d‐gal)‐induced ageing model. Results ScRNA‐seq totally figured out five cell types including myo‐lineage cells and FAPs, and myo‐lineage cells were further classified into six subpopulations, termed as RCN3+, S100A4+, ID3+, cycling (MKI67+), MYF6+ and MYMK+ satellite cells, respectively. There was a higher proportion of cycling and MYF6+ cells in the SOL population. CellChat analysis uncovered a particular impact of FAPs on myogenic cells mediated by FGF7, which was relatively highly expressed in SOL samples. Administration of FGF7 (10 ng/mL) significantly increased the proportion of EdU+ porcine MuSCs and C2C12 by 4.03 ± 0.81% (P

Abstract The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Abstract In the quest to enhance Zn–air batteries (ZABs) for operating across a wide spectrum of temperatures, synthesizing robust oxygen electrocatalysts is paramount. Conventional strategies focusing on orbital hybridization of d–d and p‐d aim to moderate the excessive interaction between the d‐band of the transition metal active site and oxygen intermediate, yet often yield suboptimal performance. Herein, an innovative s‐block metal modulation is reported to refine the electronic structure and catalytic behavior of Co─NC catalysts. Employing density functional theory (DFT) calculations, it is revealed that incorporating Mg markedly depresses the d‐band center of Co sites, thereby fine‐tuning the adsorption energy of the oxygen reduction reaction (ORR) intermediate. Consequently, the Mg‐modified Co─NC catalyst (MgCo─NC) unveils remarkable intrinsic ORR activity with a significantly reduced activation energy (Ea) of 10.0 kJ mol−1, outstripping the performance of both Co─NC (17.6 kJ mol−1), benchmark Pt/C (15.9 kJ mol−1), and many recent reports. Moreover, ZABs outfitted with the finely tuned Mg0.1Co0.9─NC realize a formidable power density of 157.0 mW cm−2, paired with an extremely long cycle life of 1700 h, and an exceptionally minimal voltage gap decay rate of 0.006 mV h−1. Further, the Mg0.1Co0.9─NC‐based flexible ZAB presents a mere 2% specific capacity degradation when the temperature fluctuates from 25 to −20 °C, underscoring its robustness and suitability for practical deployment in diverse environmental conditions.

BackgroundCognitive impairment (CI) is common in Parkinson’s disease (PD). Multiple brain regions and their interactions are involved in PD associated CI. Magnetic resonance imaging (MRI) technology is a non-invasive method in investigating brain structure and inter-regional connections. In this study, by comparing cortical thickness, subcortical volume, and brain network topology properties in PD patients with and without CI, we aimed to understand the changes of brain structure and structural covariance network properties in PD associated CI.MethodsA total of 18 PD patients with CI and 33 PD patients without CI were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr stage, Mini Mental State Examination Scale, Non-motor Symptom Rating Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were assessed. All participants underwent structural 3T MRI. Cortical thickness, subcortical volume, global and nodal network topology properties were measured.ResultsCompared with PD patients without CI, the volumes of white matter, thalamus and hippocampus were lower in PD patients with CI. And decreased whole-brain local efficiency is associated with CI in PD patients. While the cortical thickness and nodal network topology properties were comparable between PD patients with and without CI.ConclusionOur findings support the alterations of brain structure and disruption of structural covariance network are involved in PD associated CI, providing a new insight into the association between graph properties and PD associated CI.

Abstract Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by dynamin-like GTPase atlastin (ATL). This fundamental process relies on GTP-dependent domain rearrangements in the N-terminal region of ATL (ATLcyto), including the GTPase domain and three-helix bundle (3HB). However, its conformational dynamics during the GTPase cycle remain elusive. Here, we combine single-molecule FRET imaging and molecular dynamics simulations to address this conundrum. Different from the prevailing model, ATLcyto can form a loose crossover dimer upon GTP binding, which is tightened by GTP hydrolysis for membrane fusion. Furthermore, the α-helical motif between the 3HB and transmembrane domain, which is embedded in the surface of the lipid bilayer and self-associates in the crossover dimer, is required for ATL function. To recycle the proteins, Pi release, which disassembles the dimer, activates frequent relative movements between the GTPase domain and 3HB, and subsequent GDP dissociation alters the conformational preference of the ATLcyto monomer for entering the next reaction cycle. Finally, we found that two disease-causing mutations affect human ATL1 activity by destabilizing GTP binding-induced loose crossover dimer formation and the membrane-embedded helix, respectively. These results provide insights into ATL-mediated homotypic membrane fusion and the pathological mechanisms of related disease.

ABSTRACT: Calf diarrhea, a common disease mainly induced by Escherichia coli infection, is one of the main reasons for nonpredator losses. Hence, an effective nonantibacterial approach to prevent calf diarrhea has become an emerging requirement. This study evaluated the microalgae Schizochytrium sp. (SZ) and lactoferrin (LF) as a nutrient intervention approach against E. coli O101:K99-induced preweaning calve diarrhea. Fifty 1-d-old male Holstein calves were randomly divided into 5 groups (n = 10): (1) control, (2) blank (no supplement or challenge), (3) 1 g/d LF, (4) 20 g/d SZ, or (5) 1 g/d LF plus 20 g/d SZ (LFSZ). The experimental period lasted 14 d. On the morning of d 7, calves were challenged with 1 × 1011 cfu of E. coli O101:K99, and rectum feces were collected on 3, 12, 24, and 168 h postchallenge for the control, LF, SZ, and LFSZ groups. The rectal feces of the blank group were collected on d 14. Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). The E. coli K99 challenge decreased the average daily gain (ADG) and increased feed-to-gain ratio (F:G) and diarrhea frequency (control vs. blank). Compared with the control group, the LFSZ group had a higher ADG and lower F:G, and the LFSZ and SZ groups had lower diarrhea frequency compared with the control group. In addition, the LFSZ and SZ groups have no differences in diarrhea frequency compared with the blank group. Compared with the control group, the blank group had lower serum nitric oxide (NO), endothelin-1, d-lactic acid (D-LA), and lipopolysaccharide (LPS) concentrations, as well as serum IgG, IL-1β, IL-6, IL-10, and TNF-α levels on d 7 and 14. On d 7, compared with the control group, all treatment groups had lower serum NO level, the SZ group had a lower serum D-LA concentration, and the LF and LFSZ groups had lower serum LPS concentration. On d 14, compared with the control group, the fecal microbiota of the blank group had lower Shannon, Simpson, Chao1, and ACE indexes, the LFSZ group had lower Shannon and Simpson indexes, the SZ and LFSZ groups had a higher Chao1 index, and all treatment groups had a higher ACE index. In fecal microbiota, Bifidobacterium and Actinobacteria were negatively associated with IL-10 and d-lactate, while Akkermansia was negatively associated with endothelin-1 and positively correlated with LPS, fecal scores, and d-lactate levels. Our results indicated that LF and SZ supplements could alleviate E. coli O101:K99-induced calf diarrhea individually or in combination. Supplementing 1 g/d LF and 20 g/d SZ could be a potential nutrient intervention approach to prevent bacterial diarrhea in calves.

The damage evolution process of non-penetrating cracks often causes some unexpected engineering disasters. Gypsum specimens containing non-penetrating crack(s) are used to study the damage evolution and characteristics under cyclic loading. The results show that under cyclic loading, the relationship between the number of non-penetrating crack(s) and the characteristic parameters (cyclic number, peak stress, peak strain, failure stress, and failure strain) of the pre-cracked specimens can be represented by a decreasing linear function. The damage evolution equation is fitted by calibrating the accumulative plastic strain for each cycle, and the damage constitutive equation is proposed by the concept of effective stress. Additionally, non-penetrating cracks are more likely to cause uneven stress distribution, damage accumulation, and local failure of specimen. The local failure can change the stress distribution and relieve the inhibition of non-penetrating crack extension and eventually cause a dramatic destruction of the specimen. Therefore, the evolution process caused by non-penetrating cracks can be regarded as one of the important reasons for inducing rockburst. These results are expected to improve the understanding of the process of spalling formation and rockburst and can be used to analyze the stability of rocks or rock structures.

Abstract The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway.

Abstract Background The biological behavior of low-grade glioma (LGG) is significantly affected by N6-methyladenosine (m6A) methylation, an essential epigenetic alteration. Therefore, it is crucial to create a prognostic model for LGG by utilizing genes that regulate m6A methylation. Methods Using TCGA and GTEx databases. We examined m6A modulator levels in LGG and normal tissues, and investigated PD-L1 and PD-1 expression, immune scores, immune cell infiltration, tumor immune microenvironment (TIME) and potential underlying mechanisms in different LGG clusters. We also performed immunohistochemistry and RT-qPCR to identify essential m6A adjustment factor. Results The results showed that m6A regulatory element expression was significantly increased in LGG tissues and was significantly associated with TMIE. A substantial increase in PD-L1 and PD-1 levels in LGG tissues and high-risk cohorts was observed. PD-L1 expression was positively correlated with FTO, ZCCHC4, and HNRNPD, whereas PD-1 expression was negatively correlated with FTO, ZC3H7B, and HNRNPD. The prognostic signature created using regulators of m6A RNA methylation was shown to be strongly associated with the overall survival of LGG patients, and FTO and ZCCHC4 were confirmed as independent prognostic markers by clinical samples. Furthermore, the results revealed different TIME characteristics between the two groups of patients, indicating disrupted signaling pathways associated with LGG. Conclusion Our results present that the m6A regulators play vital role in regulating PD-L1/PD-1 expression and the infiltration of immune cells, thereby exerting a sizable impact on the TIME of LGG. Therefore, m6A regulators have precise predictive value in the prognosis of LGG.

Abstract Background The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis. Methods A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients’ baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models. Results Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P

Currently, brain-computer interface technology still poses hidden dangers in the complete control of ideas. Additionally, there are issues with the low sampling frequency and accuracy of EEG signal acquisition equipment. To address these concerns, this study proposes a combined model for EEG signal recognition and classification analysis by combining frequency division multi-feature complex brain networks with parallel convolutional neural networks. The effectiveness of this model has been verified. In model visualization analysis, the visualization results of t-distribution random neighborhood embedding in the third separable convolutional layer indicate that the two types of imagination have already experienced separation. There is a clear boundary between the two at position 0 on both the horizontal and vertical axes. This is a significant improvement compared to the comparative model. In the model performance verification, the full band classification accuracy in the synchronous network was maintained between 60% to 84%, and the $\mu $ -rhythm was maintained between 59% to 81%. The average classification accuracy of the combined model was 77.40% with higher performance, which was higher than 68.53% and 70.87% of the single scale convolutional neural network. In comparison with deep learning algorithms, the average classification accuracy of the combined model was 85.74%, much higher than the 66.20% and 76.69% of the comparative models. The composite model constructed has good performance in recognizing and classifying electroencephalogram signals. It can be effectively applied in practical brain-computer interface technology or electroencephalogram signal analysis. The potential application area of this study in the future is the recognition and processing of complex EEG signals in medical institutions, which can improve the efficiency of signal processing in this field and reduce the manpower expenditure of medical personnel.

Abstract Background The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P

Abstract Lithium-ion batteries play a crucial role in decarbonizing transportation and power grids, but their reliance on high-cost, earth-scarce cobalt in the commonly employed high-energy layered Li(NiMnCo)O2 cathodes raises supply-chain and sustainability concerns. Despite numerous attempts to address this challenge, eliminating Co from Li(NiMnCo)O2 remains elusive, as doing so detrimentally affects its layering and cycling stability. Here, we report on the rational stoichiometry control in synthesizing Li-deficient composite-structured LiNi0.95Mn0.05O2, comprising intergrown layered and rocksalt phases, which outperforms traditional layered counterparts. Through multiscale-correlated experimental characterization and computational modeling on the calcination process, we unveil the role of Li-deficiency in suppressing the rocksalt-to-layered phase transformation and crystal growth, leading to small-sized composites with the desired low anisotropic lattice expansion/contraction during charging and discharging. As a consequence, Li-deficient LiNi0.95Mn0.05O2 delivers 90% first-cycle Coulombic efficiency, 90% capacity retention, and close-to-zero voltage fade for 100 deep cycles, showing its potential as a Co-free cathode for sustainable Li-ion batteries.

Abstract Li metal batteries using Li metal as negative electrode and LiNi1-x-yMnxCoyO2 as positive electrode represent the next generation high-energy batteries. A major challenge facing these batteries is finding electrolytes capable of forming good interphases. Conventionally, electrolyte is fluorinated to generate anion-derived LiF-rich interphases. However, their low ionic conductivities forbid fast-charging. Here, we use CsNO3 as a dual-functional additive to form stable interphases on both electrodes. Such strategy allows the use of 1,2-dimethoxyethane as the single solvent, promising superior ion transport and fast charging. LiNi1-x-yMnxCoyO2 is protected by the nitrate-derived species. On the Li metal side, large Cs+ has weak interactions with the solvent, leading to presence of anions in the solvation sheath and an anion-derived interphase. The interphase is surprisingly dominated by cesium bis(fluorosulfonyl)imide, a component not reported before. Its presence suggests that Cs+ is doing more than just electrostatic shielding as commonly believed. The interphase is free of LiF but still promises high performance as cells with high LiNi0.8Mn0.1Co0.1O2 loading (21 mg/cm2) and low N/P ratio (~2) can be cycled at 2C (~8 mA/cm2) with above 80% capacity retention after 200 cycles. These results suggest the role of LiF and Cs-containing additives need to be revisited.

BackgroundArsenic exposure can lead to liver dysfunction, liver steatosis, hepatitis, liver fibrosis, and other liver injuries, but its mechanism is still unclear and effective treatment methods are lacking.ObjectiveTo investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine (SAM) metabolism.MethodsThirty-six Wistar rats were randomly divided into six groups, six rats in each group, half male and half female. The low, medium, and high dose groups of sodium arsenite (NaAsO2) were given 2.5, 5.0, and 10.0 NaAsO2 mg·kg−1 (body weight, thereafter), respectively; the control group was given 10 mL·kg−1 deionized water; the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg−1 NaAsO2 for 4 h and then 10 mL·kg−1 Rosa roxburghii Tratt juice; the Rosa roxburghii Tratt juice control group was given 10 mL·kg−1 Rosa roxburghii Tratt juice by gavage. All rats were gavaged once a day, 6 d per week for 4 months. Histopathological changes of rat liver were observed by hematoxylin-eosin (HE) staining. Total bile acids (TBA) and γ-glutamyl transpeptidase (γ-GT) were detected by enzyme cycle method and rate method, respectively. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was used to evaluate SAM and S-adenosylhomo cysteine (SAH) in rat liver. Real-time fluorescence quantitative reverse transcriptional PCR (RT-qPCR) was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase (Gnmt), nicotinamide-N-methyltransferase (Nnmt), and phosphatidylethano-lamine N-mathyltransferase (Pemt).ResultsIn the control group, the liver nuclei were stained clearly, the cytoplasm was stained uniformly, and the liver cords were arranged radially without inflammatory infiltration. In the low, medium, and high dose groups of NaAsO2, hepatic sinusoidal dilation, congestion, and inflammatory infiltration were observed to different degrees. Compared with the control group, TBA in the medium and high dose groups of NaAsO2, and γ-GT in the high dose group of NaAsO2 were significantly increased (P

Abstract Single-atom catalysts (SACs) are particularly sensitive to external conditions, complicating the identification of catalytically active species and active sites under in situ or operando conditions. We developed a methodology for tracing the structural evolution of SACs to nanoparticles, identifying the active species and their link to the catalytic activity for the reverse water gas shift (RWGS) reaction. The new method is illustrated by studying structure-activity relationships in two materials containing Pt SACs on ceria nanodomes, supported on either ceria or titania. These materials exhibited distinctly different activities for CO production. Multimodal operando characterization attributed the enhanced activity of the titania-supported catalysts at temperatures below 320 ˚C to the formation of unique Pt sites at the ceria-titania interface capable of forming Pt nanoparticles, the active species for the RWGS reaction. Migration of Pt nanoparticles to titania support was found to be responsible for the deactivation of titania-supported catalysts at elevated temperatures. Tracking the migration of Pt atoms provides a new opportunity to investigate the activation and deactivation of Pt SACs for the RWGS reaction.

IntroductionMedicinal plants, rich in phytochemicals like phenolic acids, flavonoids, and tannins, offer potential benefits in enhancing productivity, quality, and animal health. Amla fruit (Phyllanthus emblica) is one such plant with promising attributes. This study aimed to investigate the impact of fresh Amla fruit (FAF) supplementation on ruminal microbial composition and its correlation with rumen fermentation in lactating dairy cows.MethodsThe study employed a repeated crossover design involving eight ruminally cannulated mid-lactation Holstein dairy cows. Animals received varying levels of fresh Amla fruit supplementation (0, 200, 400, and 600 g/d).ResultsWhen 400 g/d of FAF was added to the diet, there was a significant increase in the relative abundance of Firmicutes (p = 0.02). However, at 200 g/d, the relative abundance of ruminal Bacteroidota was higher than the 0 and 400 g/d FAF supplementation (p

Abstract Hydrocephalus is one of the most common brain disorders and a life‐long incurable condition. An empirical “one‐size‐fits‐all” approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage‐mediated ChP inflammation and CSF hypersecretion have recently been identified as a significant discovery in the pathogenesis of hydrocephalus. In this study, a pioneering DNA nano‐drug (TSOs) is developed by modifying S2 ssDNA and S4 ssDNA with SPAK ASO and OSR1 ASO in tetrahedral framework nucleic acids (tFNAs) and synthesis via a one‐pot annealing procedure. This construct can significantly knockdown the expression of SPAK and OSR1, along with their downstream ion channel proteins in ChP epithelial cells, thereby leading to a decrease in CSF secretion. Moreover, these findings indicate that TSOs effectively inhibit the M0 to M1 phenotypic switch of ChP macrophages via the MAPK pathways, thus mitigating the cytokine storm. In in vivo post‐hemorrhagic hydrocephalus (PHH) models, TSOs significantly reduce CSF secretion rates, alleviate ChP inflammation, and prevent the onset of hydrocephalus. These compelling results highlight the potential of TSOs as a promising therapeutic option for managing hydrocephalus, with significant applications in the future.

Calotropis gigantea (Giant milkweed, GM) has the potential to be utilized as a new feed additive for ruminants, however, the presence of unpalatable or toxic compounds decreases animal feed intake. This study aimed to valorize GM as a potential new feed resource through the chemical and microbial biotransformation of toxic compounds that will henceforth, make the plant palatable for cows. After GM’s ensiling using fermentative bacteria, the plant was sampled for UHPLC-MS/MS to analyse the metabolomic changes. Illumina Miseq of the 16 S rRNA fragment genes and ITS1 were used to describe the microbial composition and structure colonizing GM silage and contributing to the biodegradation of toxic compounds. Microbial functions were predicted from metataxonomic data and KEGG pathways analysis. Eight Holstein dairy cows assigned in a cross-over design were supplemented with GM and GM silage to evaluate palatability and effects on milk yield and milk protein. Cows were fed their typical diet prior to the experiment (positive control). After ensiling, 23 flavonoids, 47 amino acids and derivatives increased, while the other 14 flavonoids, 9 amino acids and derivatives decreased, indicating active metabolism during the GM ensiling process. Lactobacillus buchneri, Bacteroides ovatus, and Megasphaera elsdenii were specific to ensiled GM and correlated to functional plant metabolites, while Sphingomonas paucimobilis and Staphylococcus saprophyticus were specific to non-ensiled GM and correlated to the toxic metabolite 5-hydroxymethylfurfural.''Xenobiotics biodegradation and metabolism'', ''cancer overview'' and ''neurodegenerative disease'' were the highly expressed microbial KEGG pathways in non-ensiled GM. Non-ensiled GM is unpalatable for cows and drastically reduces the animal’s feed intake, whereas ensiled GM does not reduce feed intake, milk yield and milk protein. This study provides essential information for sustainable animal production by valorizing GM as a new feed additive.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Abstract Introduction There are only four sizes of implantable collamer lens (ICL) available for selection, which cannot completely fit all patients as a result of the discontinuity of ICL sizes. Sizing an optimal ICL and predicting postoperative vault are still unresolved problems. This study aimed to develop and validate innovative data-level data-balancing machine learning-based models for predicting ICL size and postoperative vault. Methods The patients were randomly assigned to training and internal validation sets in a 4:1 ratio. Feature selection was performed using analysis of variance (ANOVA) and Kruskal–Wallis feature importance methods. Traditional linear regression model and machine learning-based models were used. The accuracy of models was assessed using the area under the curve (AUC) and confusion matrix. Results A total of 564 patients (1127 eyes) were eligible for this study, consisting of 808 eyes in the training set, 202 eyes in the internal validation set, and 117 eyes in the external validation set. Compared with the traditional linear regression method, the machine learning model bagging tree showed the best performance for ICL size selection, with an accuracy of 84.5% (95% confidence interval (CI) 83.2–85.8%), and the AUC ranged from 0.88 to 0.99; the prediction accuracy of 12.1 mm and 13.7 mm ICL sizes was improved by 49% and 59%, respectively. The bagging tree model achieved the best accuracy [90.2%, (95% CI 88.9–91.5%)] for predicting the postoperative vault, and the AUC ranged from 0.90 to 0.94. The prediction accuracies of internal and external validation dataset for ICL sizing were 82.2% (95% CI 81.1–83.3%) and 82.1% (95% CI 81.1–83.1%), respectively. Conclusions The innovative data-level data balancing-based machine learning model can be used to predict ICL size and postoperative vault more accurately, which can assist surgeons in choosing optimal ICL size, thus reducing risks of postoperative complications and secondary surgery.

Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

In this work, a new model to analyse the dynamic characteristic coefficient of the S-CO2 dry gas seal was reported. Taking into account that the flow within the S-CO2 dry gas seal is close to adiabatic flow, the impact of the temperature change on the dynamic characteristic coefficient of the gas film cannot be ignored. To address this issue, a complete variable perturbation model (CVPM) under the adiabatic flow process was established using the frequency perturbation method while considering multiple complex effects. Then, the finite difference method was used to solve the CVPM. The gas film’s dynamic stiffness and damping coefficients were calculated and analysed for different conditions, operating parameters, and frequency ratios. From our analysis, it was demonstrated that the dynamic coefficient of the gas film exhibited frequency dependence. The turbulence coefficient perturbation had the most remarkable influence on the gas film’s dynamic coefficient, compared to the temperature, viscosity, and centrifugal inertia force perturbations. The isothermal flow, adiabatic flow, inlet pressure, and inlet temperature also affected the magnitude of the dynamic characteristic coefficient of the gas film. However, no significant impact on their tendency to vary with the frequency ratio was found. Our work provides new theoretical support for the dynamic analysis of S-CO2 dry gas seals, which is of great importance for future applications.

Groundwater Contamination Source Identification (GCSI) is a crucial prerequisite for conducting comprehensive pollution risk assessments, formulating effective groundwater contamination control strategies, and devising remediation plans. In previous GCSI studies, various boundary conditions were typically assumed to be known variables. However, in many practical scenarios, these boundary conditions are exceedingly complex and difficult to accurately pre-determine. This practice of presuming boundary conditions as known may significantly deviate from reality, leading to errors in identification results. Moreover, the outcomes of GCSI may be influenced by multiple factors or conditions, including the fundamental information about the contamination source boundary conditions of the polluted area. This study primarily focuses on contamination source information and unknown boundary conditions. Innovatively, three deep learning surrogate models, the Deep Belief Neural Network (DBNN), Bidirectional Long Short-Term Memory Networks (BiLSTM), and Deep Residual Neural Network (DRNN), are employed for identification and validation and to simulate the highly no-linear simulation model and directly establish a mapping relationship between the outputs and inputs of the simulation model. This approach enables the direct acquisition of the inverse identification results of the variables based on actual monitoring data, thereby facilitating rapid inverse identification. Furthermore, to account for the uncertainty of noise in monitoring data, the inversion accuracy of these three deep learning methods is compared, and the method with higher accuracy is selected for uncertainty analysis. Multiple experiments were conducted, such as accuracy identification tests, robustness tests, and cross-comparative ablation studies. The results demonstrate that all three deep learning models effectively complete the research tasks, with DBNN showing the most exceptional performance in the experiments. DBNN achieved an R2 value of 0.982, an RMSE of 3.77, and an MAE of 7.56%. Subsequent uncertainty analysis, model robustness, and ablation study further affirm DBNN adaptability to GCSI research tasks.

The sclerotia of Wolfiporia hoelen (Fr.) Y.C. Dai & V. Papp is an important traditional Chinese medicine with diverse pharmacological properties. This study utilized a combination of PacBio Long-Read Sequencing, Illumina Short-Read Sequencing, and Hi-C Sequencing to generate a high-quality chromosome-level genome assembly of a W. hoelen strain Minling A5. There were 112 contigs in the genome, with 62.95 Mb in total length and 4.21 Mb in length for the contig N50. The average GC content was 51.89%. Based on Hi-C data, we corrected the CCS data and scaffolded them into 14 pseudo-chromosomes. The genome contained 44.37% repetitive sequences and 12,670 protein-coding genes, 86.53% (10,963) of which could be functionally annotated in at least one of the KOG, GO, Pfam, Swissprot, TrEMBL, NR, and KEGG databases. In addition, 240 transfer RNAs, 97 ribosomal RNAs, and 103 other non-coding RNAs were identified in the W. hoelen genome. A total of 755 pseudogenes were also identified, with an average length of 2665.51 bp. Further, there were 398, 100, 2837, 519, and 2068 genes annotated by CAZymes, TCDB, PHI, P450, and DFVF databases, respectively. One notable attribute of W. hoelen is its capacity to thrive in a substrate of fresh pine sawdust. Through an analysis of the growth on various pure wood sawdust culture media, we found that the growth of W. hoelen and Sparassis latifolia on pine sawdust was similar to that on broad-leaved wood sawdust, while the growth of Pleurotus ostreatus, P. eryngii, and Cyclocybe aegerita was slower than that on broad-leaved wood sawdust. By the functional annotation analysis of orthogroups in these five mushroom-forming fungi, it was determined that 645 orthogroups were specifically common in W. hoelen and S. latifolia. The genes in these specific orthogroups were significantly enriched in 12 pathways, including steroid biosynthesis, biosynthesis of antibiotics, and tyrosine metabolism. The high-quality genome and comparative genome analysis results significantly contribute to advancing our foundational knowledge of W. hoelen biology, while also offering valuable insights for the development of innovative biotechnological approaches aimed at enhancing the efficient and sustainable utilization of Pinus.

BackgroundCurrent evidence linking sedentary behavior (SB), physical activity (PA), and inflammation raises questions about their causal relationships, prompting concerns about potential residual confounding or reverse causation.MethodsA bidirectional Mendelian randomization (MR) analysis was conducted. SB data (n = 408,815) from "computer use," "television watching," and "driving" were included. The PA data encompassed nine types of PA (n = 460,376) over the last four weeks and included data on the frequency of vigorous PA (n = 440,512) and moderate PA (n = 440,266) for over 10 min. Additionally, three genome-wide association study datasets (n = 64,949) on light, moderate, and vigorous exercise were included to minimize potential bias from changes in exercise intensity. Inflammation data included levels of C-reactive protein (CRP) (n = 575,531), glycoprotein acetyl (GlycA) (n = 115,082), interleukin (IL)-8, IL-6, IL-6 receptor (IL-6R), and soluble IL-6R (sIL-6R) (n = 35,278). All datasets represented participants of European ancestry.ResultsTelevision watching as an SB showed significant positive causal effects on GlycA and CRP (inverse variance weighted (IVW), odds ratios (OR): 1.34, 95% confidence intervals (CI): 1.25-1.44, p = 3.570 × 10-17; IVW, OR: 1.21, 95% CI: 1.16-1.26, p = 1.500 × 10-19, respectively), with more robust evidence for GlycA. In the direction from inflammation to PA, a negative causal relationship between CRP and"number of days/week of moderate PA 10+ minutes"was observed (IVW, OR: 0.92, 95% CI: 0.89-0.96, p = 3.260 × 10-5). Sensitivity analyses were used to verify the robustness and reliability of the results. However, other initially observed associations ceased to be significant after controlling for obesity-related confounders.ConclusionOur MR analysis suggested a potential causal relationship between television watching and chronic low-grade inflammation, with more substantial evidence for GlycA. Additionally, different types of SB may have varying effects on inflammation. Obesity-related traits could partly or entirely influence the relationship between SB, PA, and inflammatory markers. Furthermore, Our findings indicate that SB is an independent risk factor for inflammation, separate from PA, and highlight the different mechanisms by which SB and PA affect disease.

ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

The domestic sewage in rural areas of South China is characterized by a relatively low concentration of organic pollutants; however, the factors causing this have not been carefully examined. This study conducted a comprehensive survey on two sewer networks in a small town of Eastern Guangdong, China, via grab water sampling at a frequency of once every 2 weeks lasting for 1 year. The sewage quality showed significant variations across the systems, while a gradual decrease in the concentrations of chemical oxygen demand (COD), total nitrogen (TN) and phosphorus (TP) from the upper to lower reaches of sewers could be observed. Storm events could have a flushing effect on TP in the upper reach of sewers, but a dilution effect on COD and TN in flat terrains. The diurnal pattern of sewage was largely impacted by the position of the manholes and water consumption difference between holidays and normal days. Both COD/TN and TN/TP ratios of the sewage showed a lognormal distribution dominating in the range of 2.0–3.0 and ~10.0, respectively. The low ratio of COD/TN in the morning discharge peak could be attributed to the wide use of septic tanks in the area, while groundwater infiltration played more important roles in the basal flow conditions. This study could serve as a basic reference for designing and managing sewage infrastructure in rural areas of South China and highlights that prevention of groundwater infiltration is crucial to improve the efficiency of sewage infrastructure in high water table areas.

Underwater acoustic (UWA) channel prediction technology, as an important topic in UWA communication, has played an important role in UWA adaptive communication network and underwater target perception. Although many significant advancements have been achieved in underwater acoustic channel prediction over the years, a comprehensive summary and introduction is still lacking. As the first comprehensive overview of UWA channel prediction, this paper introduces past works and algorithm implementation methods of channel prediction from the perspective of linear, kernel-based, and deep learning approaches. Importantly, based on available at-sea experiment datasets, this paper compares the performance of current primary UWA channel prediction algorithms under a unified system framework, providing researchers with a comprehensive and objective understanding of UWA channel prediction. Finally, it discusses the directions and challenges for future research. The survey finds that linear prediction algorithms are the most widely applied, and deep learning, as the most advanced type of algorithm, has moved this field into a new stage. The experimental results show that the linear algorithms have the lowest computational complexity, and when the training samples are sufficient, deep learning algorithms have the best prediction performance.

This study aimed at evaluating the milk production after supplementing Calotropis gigantea (Giant milkweed, GM) silage as a new functional feed additive for ruminants. Cows refused to eat GM plants so, we processed it into silage before feeding. After ensiling, six ruminally cannulated dairy cows were assigned to two treatment groups (GM silage supplementation treatment and control without GM silage supplementation) in a cross over design. Repeated sampling of milk and rumen fluid was carried out on the last days of the third and fourth week after treatment. Ensiling GM increased the crude proteins, neutral detergent fiber and acid detergent fiber while ash was unchanged. There was no dry matter intake (DMI) when supplementing GM forage to the cows, DMI and milk yield returned to normal conditions but feed efficiency, milk protein, milk fat and lactose slightly increased when supplementing GM silage. Rumen protozoa genera such as Entodinium, Ophryoscolex, Eudiplodinium, Dasytricha and Isotricha were maintained. A dose effect study remained to be carried out to identify an effective dose that could bring significant enhancement of the animal production after supplementing GM silage. This study revealed that the silage form of GM can be a new source of proteins for dairy cows and an appropriate dose could potentially induce some improvement of the milk production and composition. Therefore, the plant will not continue to be perceived as an invasive weed but as a new forage to be integrated into the cow’s diet.

As the only alkaline polysaccharide in nature, chitosan(CTS) is haracterized by its unique physiological activity, good film-forming capacity, well adsorption and antibacterial properties. Various pharmaceutical preparations and clinical applications of CTS and its derivatives have proved the practicability of CTS products in the field of pharmaceutical preparations. CTS and its derivatives have a good development prospect in the field of medicine and clinical application.

Abstract Objective The relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients. Methods Several online databases including Ovid MEDILNE, Ovid EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 15, 2022. We included randomized clinical trials (RCT) of adult migraine patients with previous treatment failure that assessed any CGRP monoclonal antibody. The primary efficacy outcome was change in monthly migraine days (MMDs), and the primary safety outcome was treatment-emergent adverse events (TEAEs). Results Overall, seven studies totaling 3, 052 patients were included. Three-node analysis showed that CGRP mAbs was superior to CGRP receptor mAbs in reducing MMDs (MD: -1.55, 95% CrI: − 2.43 to − 0.44) and improving at least 50% response rates (RR: 1.52, 95% CrI: 1.04 to 2.21). Nine-node analysis showed galcanezumab 240 mg ranked first in reducing MMDs (MD -4.40, 95% CrI − 7.60 to − 1.19) and improving 50% response rates (RR: 4.18, 95% CrI: 2.63 to 6.67). Moreover, treatment with fremanezumab or eptinezumab 300 mg provides a significant advantage over erenumab 140 mg regarding an improved response rate of at least 50%. The analysis did not show difference in incidences of TEAEs and serious adverse events in any of the comparisons. Conclusions It appears that CGRP mAbs, especially galcanezumab 240 mg, monthly fremanezumab, and eptinezumab 300 mg, seem to be the best choice for the treatment of migraine patients with previous treatment failures. This finding also calls for future research that examine the associations between these medications in migraine therapy among the same patient group to testify the present findings.

Catalytic pathways of plastic waste valorization to lubricants are attractive avenues to foster circular economy. Tuning of catalyst electronic properties allows to significantly improve its activity due to boosted hydrogen storage on the surface.

Diet plays a crucial role in shaping the gut microbiota and overall health of animals. Traditionally, silkworms are fed fresh mulberry leaves, and artificial diets do not support good health. The aim of this study was to explore the relationship between the dietary transition from artificial diets to mulberry leaves and the effects on the gut microbiota and physiological changes in silkworms as a model organism. With the transition from artificial diets to mulberry leaves, the diversity of the silkworm gut microbiota increased, and the proportion of Enterococcus and Weissella, the dominant gut bacterial species in silkworms reared on artificial diets, decreased, whereas the abundance of Achromobacter and Rhodococcus increased. Dietary transition at different times, including the third or fifth instar larval stages, resulted in significant differences in the growth and development, immune resistance, and silk production capacity of silkworms. These changes might have been associated with the rapid adaptation of the intestinal microbiota of silkworms to dietary transition. This study preliminarily established a dietary transition–gut microbial model in silkworms based on the conversion from artificial diets to mulberry leaves, thus providing an important reference for future studies on the mechanisms through which habitual dietary changes affect host physiology through the gut microbiome.

Rice blast is one of the most devastating diseases, causing a significant reduction in global rice production. Developing and utilizing resistant varieties has proven to be the most efficient and cost-effective approach to control blasts. However, due to environmental pressure and intense pathogenic selection, resistance has rapidly broken down, and more durable resistance genes are being discovered. In this paper, a novel wall-associated kinase (WAK) gene, Pb4, which confers resistance to rice blast, was identified through a genome-wide association study (GWAS) utilizing 249 rice accessions. Pb4 comprises an N-terminal signal peptide, extracellular GUB domain, EGF domain, EGF-Ca2+ domain, and intracellular Ser/Thr protein kinase domain. The extracellular domain (GUB domain, EGF domain, and EGF-Ca2+ domain) of Pb4 can interact with the extracellular domain of CEBiP. Additionally, its expression is induced by chitin and polygalacturonic acid. Furthermore, transgenic plants overexpressing Pb4 enhance resistance to rice blast. In summary, this study identified a novel rice blast-resistant gene, Pb4, and provides a theoretical basis for understanding the role of WAKs in mediating rice resistance against rice blast disease.

Abstract Non-small cell lung cancer (NSCLC) is highly malignant and heterogeneous form of lung cancer and involves various oncogene alterations. Glycolysis, an important step in tumor metabolism, is closely related to cancer progression. In this study, we investigated the biological function and mechanism of action of Gankyrin in glycolysis and its association with NSCLC. Analyzed of data from The Cancer Genome Atlas as well as NSCLC specimens and adjacent tissues demonstrated that Gankyrin expression was upregulated in NSCLC tissues compared to adjacent normal tissues. Gankyrin was found to significantly aggravate cancer-related phenotypes, including cell viability, migration, invasion, and epithelial mesenchymal transition (EMT), whereas Gankyrin silencing alleviated the malignant phenotype of NSCLC cells. Our results reveal that Gankyrin exerted its function by regulating YAP1 expression and increasing its nuclear translocation. Importantly, YAP1 actuates glycolysis, which involves glucose uptake, lactic acid production, and ATP generation and thus might contribute to the tumorigenic effect of Gankyrin. Furthermore, the Gankyrin-accelerated glycolysis in NSCLC cells was reversed by YAP1 deficiency. Gankyrin knockdown reduced A549 cell tumorigenesis and EMT and decreased YAP1 expression in a subcutaneous xenograft nude mouse model. In conclusion, both Gankyrin and YAP1 play important roles in tumor metabolism, and Gankyrin-targeted inhibition may be a potential anti-cancer therapeutic strategy for NSCLC.

Abstract Background The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors. Methods Several databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events. Results Overall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72–0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04–1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90–0.99). Conclusions In consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.